Every client project is a unique proposition, hence the requirement for a collaborative approach. MicroMatrices possesses an evolving array of applications. Many of these support Mode of Action understanding, which can be used to generate hypotheses and design bespoke investigatory studies, to help develop a Threshold Based Risk Assessment and Human Relevance argument.
The SpheroMatrices® array technology (patent pending) overcomes the challenges of obtaining quantitative data in 3D spheroid/microtissue experiments by aligning all the spheroids within a 96 well plate in a plane and making simultaneous physical sections through all the tissues, whilst retaining the experimental 96 well format.
The individual sections can be immunstained for a wide variety of biological endpoint and quantitatively analysed with automated image analysis scripts . In addition, tissue from parallel sections can be laser-dissected for transcriptomic and/or proteomic analysis to provide complementary molecular profiling information within the same 96 well experiment.
SpheroMatrices potentiates drug development in human relevant 3D models by identifying and quantifying targets that would not be accessible with currently available platforms. To find out more, visit www.spheromatrices.com.
With fixed tissue samples (SpheroMatrices and FFPE) it is possible to perform repeated cycles of Heat-induced Epitope Retrieval on the samples, required for multiplexed staining, without impacting upon the integrity of the tissue. With current multiplexing protocols, it is possible to stain for up to 7 tissue biomarkers providing a powerful tool for visualising:
With SpheroMatrices all treatment groups within a 96 well experiment can be assessed simultaneously, an especially valuable capability for the study of the effects of anti-tumor candidate drugs in tumor/PDX models.
LDT facilitates focused exploration of FFPE or frozen tissues from investigative studies. The combination of laser microdissection, microarray, and molecular pathology techniques results in a powerful approach to tissue analysis for exploring molecular markers and pathway perturbations. The technique yields sufficient mRNA to enable a tissue region-specific unbiased pathways analysis for the identification of several candidate genes, and gene expression pathways for hypothesis generation and testing.
An example of this approach can be found in Case Study 2.
MicroMatrices are experts in the use of RNAscope technology, capable of detecting and visualising a single RNA transcript within a cell with high sensitivity/specificity and little to no background. This technology has now been refined to allow for the detection of a single base pair change. Used in combination with immunostaining and colocalisation analysis, RNA/Basescope offers a unique target visualisation capacity which can guide and/or corroborate mechanistic and mode of action studies. For an example of this application, please see Case Study 1.
We use automated image analysis algorithms designed to quantify target/biomarker distribution, visualised via immunostaining, within pathologically defined tissue areas; data is normalised to facilitate comparison between samples. Our WSIA flyer contains further information on the benefits of this methodology as well as a sample application.
We have developed methodologies for extracting RNA from any FFPE tissue samples for use in integrated miRNA/mRNA array investigations and unbiased and focused pathways analysis. We can then further explore molecular pathology using immunohistochemistry (IHC), RNAscope in situ hybridisation (ISH) colocalisation, image analysis, etc. These combined approaches unlock the potential of archival samples and aids the design of bespoke prospective investigative studies whilst reducing the need for new animal experiments. An example of this approach can be found in Case Study 1, and also in our white paper, produced in partnership with Zeiss.
We can support in early discovery, development, and product life cycle maintenance. Should registration concerns arise as a consequence of regulatory tests with model species, MicroMatrices can assist. We will undertake mechanism-based risk assessment analyses to investigate hypotheses of toxicity and determine whether a case for non-human relevance can be demonstrated, potentially extending the commercial life of the product.
A demonstration of this approach can be seen in Case Study 1.
MicroMatrices possess a varied and adaptable toolbox of molecular profiling techniques for the discovery of novel biomarkers for toxicity and will custom design assays to address the unique requirements of our clients. Case Study 2 provides an example of the approaches which can be used in the identification of mechanistic biomarkers within target cells.
MicroMatrices’ array of technologies are well suited to exploring and demonstrating xenobiotic targets, using both in situ hybridisation (ISH) and immune staining (IHC). The unique sensitivity of RNAscope, in particular, enables highly specific localisation. An example of the application of this approach is contained in Case Study 3, where we demonstrate the mapping of GABA isoforms.
MicroMatrices will assist in the preparation and review of manuscripts for publication, study reports, SOPs, and other technical documents; please enquire.
on an interactive, step by step basis. Collaborations can begin with pilot projects which can then be scaled up to larger research programs, according to your requirements.